[Mapping of the gene for autosomal-recessive progressive muscular dystrophy in an isolate from a highland region of Dagestan to chromosome 2-13].
A unique inbred Avar family from an isolate of the Dagestan highland was studied. Unusual phenotypic expression of autosomal recessive progressive muscular dystrophy was revealed in 12 members of this family from three generations. Limb-girdle (proximal) muscular dystrophy (LGMD) was detected in nine patients, while the other three patients displayed typical distal myopathy (DM). Genetic linkage analysis with several candidate loci determining various forms of muscular dystrophy allowed a gene for this polymorphic syndrome to be assigned to chromosome 2p13. In spite of the difference in clinical manifestation, all patients appeared to be homozygous for a unique haplotype. This implies the founder effect and proves the same genetic basis of LGMD and DM in the family. Recombination analysis showed that the centromeric and telomeric ends of the gene region are marked with D2S2111 and D2S327, respectively (genetic distance < 1 cM). This region is overlapped by two larger regions in which the genes for LGMD type 2B (LGMD2B) and Miyoshi myopathy were recently mapped. Complex analysis of clinical and genetic data indicated that LGMD2B, Miyoshi myopathy, and the revealed polymorphic syndrome may represent allelic variants of 2p13-linked autosomal recessive muscular dystrophy.
Illarioshkin
S N
SN
Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
Ivanova-Smolenskaia
I A
IA
Dimborskaia
S A
SA
Poleshchuk
V V
VV
Markova
E D
ED
Slominskiĭ
P A
PA
Bulaeva
K B
KB
Tsudzi
Sh
Sh
D000531:Altitude; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003610:Dagestan; D018450:Disease Progression; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011995:Recombination, Genetic
Kartirovanie gena autosomno-retsessivnoĭ progressiruiushcheĭ myshechnoĭ distrofii v izoliate gornogo Dagestana na khromosome 2p13.